title: Association between IL28B gene polymorphisms and plasma HCV-RNA levels in HIV/HCV-co-infected patients.
abstract: BACKGROUND
  IL28B polymorphisms influence both the rate of spontaneous hepatitis C virus (HCV) clearance and response to interferon α (IFNα)-based therapy. This observation has been reproduced in HIV-co-infected individuals. Controversy exists about the impact of IL28B alleles on HCV load.
  
  
  METHODS
  CoRIS is a nationwide, open cohort of newly diagnosed HIV-1 adults in Spain. In the subset of HCV-co-infected individuals, the relationship between plasma HCV-RNA and IL28B (rs12979860) genotypes was evaluated.
  
  
  RESULTS
  A total of 4670 HIV-1-infected patients had been included in CoRIS up to June 2010. All were naive for IFNα. HCV antibodies were reactive in 895 (19%). Of them, 289 specimens were available and tested positive for plasma HCV-RNA, with median values of 959 900 IU/ml. The rs12979860 genotype distribution in HCV viremic patients was CC 45%, CT 42.2% and TT 12.8%. The median plasma HCV-RNA according to IL28B genotypes was: CC 1 385 000, CT 848 939 and TT 251 189 IU/ml (P = 0.006). The percentage of patients with HCV-RNA more than 600 000 IU/ml was: CC 67.7%, CT 56.6% and TT 35.1% (P = 0.001). In multivariate analysis, IL28B CC/CT genotypes, infection with HCV genotypes 1/4 and prior intravenous drug users were independent predictors of HCV-RNA more than 600 000 IU/ml.
  
  
  CONCLUSIONS
  HIV/HCV-co-infected patients with the C allele (CC/CT) at rs12979860 show significantly higher plasma HCV-RNA load than TT carriers. Notably, plasma HCV-RNA levels associated with poorer response to IFNα-based therapy are significantly more frequent in CC/CT than TT carriers. Hypothetically, patients harboring the rs12979860 allele C could display a lower activity of endogenous IFNα, allowing higher HCV replication while keeping an enhanced susceptibility to exogenous IFNα therapy.
authors.affiliation: Infectious Diseases Department, Hospital Carlos III, Madrid, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Labarga
authors.forename: Vincent
authors.initials: V
authors.lastname: Soriano
authors.forename: Antonio
authors.initials: A
authors.lastname: Caruz
authors.forename: Eva
authors.initials: E
authors.lastname: Poveda
authors.forename: Federico A
authors.initials: FA
authors.lastname: Di Lello
authors.forename: Frederico
authors.initials: F
authors.lastname: Di Lello
authors.forename: Jose
authors.initials: J
authors.lastname: Hernandez-Quero
authors.forename: Santiago
authors.initials: S
authors.lastname: Moreno
authors.forename: Enrique
authors.initials: E
authors.lastname: Bernal
authors.forename: José M
authors.initials: JM
authors.lastname: Miró
authors.forename: Manuel
authors.initials: M
authors.lastname: Leal
authors.forename: Felix
authors.initials: F
authors.lastname: Gutierrez
authors.forename: Joaquín
authors.initials: J
authors.lastname: Portilla
authors.forename: Juan A
authors.initials: JA
authors.lastname: Pineda
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy / Q000235:genetics* / Q000821:virology; D000328:Adult; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000235:genetics* / Q000821:virology; D015497:HIV-1 / Q000235:genetics*; D016174:Hepacivirus / Q000235:genetics*; D006526:Hepatitis C / Q000150:complications* / Q000188:drug therapy / Q000235:genetics* / Q000821:virology; D018937:Hepatitis C Antibodies / Q000235:genetics; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012367:RNA, Viral; D011994:Recombinant Proteins; D019562:Viral Load; D014766:Viremia; D000095022:Interferon Lambda
chemical_list: D018937:Hepatitis C Antibodies; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D012367:RNA, Viral; D011994:Recombinant Proteins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda